Interpretive Summary: DNA oxidation has been known to correlate with cognitive impairment in the elderly. We examined if urinary 8-hydroxy-2-deoxyguanosine (8-OHdG), a biomarker of global DNA oxidation, was associated with cognitive function in a sample of Puerto Rican adults, who are 45-75 year old and living in the Boston and surrounding area. The cognitive function, including memory, attention, visual-spatial ability, were measured by a battery of tests. A global cognitive score, averaging performance across all cognitive tests was estimated for each subject. Urinary 8-OHdG was assessed with a monoclonal antibody ELISA kit. We found that higher 8-OHdG concentration was significantly associated with worse global cognitive scores, after adjusting for age, smoking, education, APOE status, plasma homocysteine, and other covariates (P-trend=0.01). This implies that the difference in the global score, comparing participants in the two extreme 8-OHdG quartiles, was equivalent to accelerating cognitive aging by about four years in this population. In particular, subjects with a higher DNA damage tend to have bad memory. In summary, we found that higher DNA damage (urinary 8-OHdG concentration) was associated with lower cognitive performance. Further prospective studies are needed to elucidate whether elevated urinary 8-OHdG concentrations can predict the rate of cognitive decline.

Technical Abstract:
DNA oxidative stress has been suggested as an important pathogenic mechanism in cognitive impairment and dementia. We, therefore, examined whether urinary 8-hydroxy-2-deoxyguanosine (8-OHdG), a biomarker of global DNA oxidation, was associated with cognitive function in a sample of Puerto Rican adults. We included 1003 Puerto Ricans aged 45-75 y living in the Boston and surrounding area, in the current analyses. Cognitive function was measured by using a battery of seven tests: Mini-Mental State Examination, word list learning (verbal memory), digit span (attention), clock drawing and figure copying (visual-spatial ability), and Stroop and verbal fluency tests (fluency executive functioning). The primary outcome was a global cognitive score, averaging performance across all cognitive tests. Urinary 8-OHdG was assessed with a monoclonal antibody ELISA kit.Higher 8-OHdG concentration was significantly associated with worse global cognitive scores, after adjusting for age, smoking, education, APOE status, plasma homocysteine, and other covariates (P-trend=0.01). The difference in the global score, comparing participants in the two extreme 8-OHdG quartiles, was equivalent to accelerating cognitive aging by about four years in this population. Higher 8-OHdG concentrations were also significantly associated with lower scores of word list learning, recognition, stroop, clock drawing, and weighted figure copying (P-trend <0.05 for all), but not for the remaining cognitive tests. In summary, we found that higher urinary 8-OHdG concentration was associated with lower cognitive performance. Further prospective studies are needed to elucidate whether elevated urinary 8-OHdG concentrations can predict the rate of cognitive decline.